Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE.

Published

Journal Article

PURPOSE: To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). METHODS: Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. RESULTS: Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. CONCLUSIONS: The EyeSAGE database, combining three different gene-profiling platforms including the authors' multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions.

Full Text

Duke Authors

Cited Authors

  • Bowes Rickman, C; Ebright, JN; Zavodni, ZJ; Yu, L; Wang, T; Daiger, SP; Wistow, G; Boon, K; Hauser, MA

Published Date

  • June 2006

Published In

Volume / Issue

  • 47 / 6

Start / End Page

  • 2305 - 2316

PubMed ID

  • 16723438

Pubmed Central ID

  • 16723438

International Standard Serial Number (ISSN)

  • 0146-0404

Digital Object Identifier (DOI)

  • 10.1167/iovs.05-1437

Language

  • eng

Conference Location

  • United States